Disclaimer: This comprehensive clinical reference is intended for educational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Clinical decisions must always be made by a qualified healthcare professional, considering the individual patient's circumstances and current medical guidelines. While efforts have been made to ensure accuracy, medical knowledge is constantly evolving.

Barlow's Disease: Clarification and Comprehensive Clinical Reference for Mitral Valve Prolapse (Barlow's Syndrome)

Note on Terminology: The term "Barlow's Disease" is not a recognized, singular diagnosis in modern medical nomenclature. It most commonly refers historically to Mitral Valve Prolapse (MVP), which was often called "Barlow's Syndrome" or "Floppy Mitral Valve Syndrome" after Dr. J.B. Barlow's extensive work describing the condition in the 1960s. Less commonly, "Barlow's Disease" might refer to infantile scurvy, which was described by Sir Thomas Barlow in the late 19th century as a distinct entity from adult scurvy, particularly its impact on bone development. Additionally, the Barlow maneuver is an orthopedic examination technique used to assess for developmental dysplasia of the hip in infants.

Given the typical clinical context, this comprehensive reference will focus on Mitral Valve Prolapse (MVP), also known historically as Barlow's Syndrome, as the most probable intent of "Barlow's Disease."

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Mitral Valve Prolapse (Barlow's Syndrome)

Overview

• Definition: Mitral valve prolapse (MVP) is a common valvular heart disease characterized by the displacement of one or both mitral valve leaflets into the left atrium during ventricular systole. This displacement is typically beyond the mitral annular plane. It is often, but not always, associated with myxomatous degeneration of the mitral valve leaflets and chordae tendineae, leading to redundancy and thickening of the leaflets.
• Epidemiology:
  • Prevalence: Approximately 1-3% of the general population. It is one of the most common forms of valvular heart disease.
  • Demographics: MVP affects individuals of all ages, but is often diagnosed in young to middle-aged adults (20-50 years). It shows a slight female predominance (approximately 2:1 female-to-male ratio). Familial forms exist.
• Classification:
  • Primary (Idiopathic) MVP: The most common form, occurring in the absence of other underlying systemic diseases. It is characterized by myxomatous degeneration of the mitral valve.
    • Classic MVP: Leaflet thickness ≥5 mm with ≥2 mm systolic displacement of one or both leaflets into the left atrium (best visualized in the parasternal long-axis view on echocardiography).
    • Non-classic MVP: Leaflet thickness <5 mm with ≥2 mm systolic displacement.
  • Secondary MVP: Associated with other connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta), muscular dystrophies, inherited cardiomyopathies, or rheumatic heart disease.

Pathophysiology

• Mechanism: The hallmark of MVP is myxomatous degeneration, a process where the normal collagen and elastin within the mitral valve leaflets are replaced by an excess of mucopolysaccharide-rich ground substance. This leads to:
  1. Leaflet Redundancy and Thickening: The leaflets become elongated, thickened, and often scalloped.
  2. Chordal Elongation and Rupture: The chordae tendineae, which anchor the leaflets, may become elongated, leading to excessive leaflet motion, or in severe cases, rupture, causing acute mitral regurgitation.
  3. Annular Dilation: The mitral annulus may dilate, further contributing to leaflet prolapse and incomplete coaptation. - During ventricular systole, increased intraventricular pressure causes the weakened, redundant leaflets to bow or prolapse into the left atrium. This may or may not result in mitral regurgitation, depending on the degree of leaflet coaptation.
• Risk Factors:
  • Genetic Predisposition: Family history of MVP. Specific genetic loci have been implicated (e.g., DZIP1, MYH11).
  • Connective Tissue Disorders: Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum.
  • Skeletal Abnormalities: Pectus excavatum, scoliosis, straight back syndrome.
  • Other Syndromes: Polycystic kidney disease, muscular dystrophies, Ebstein anomaly (less common association).
  • Age: Risk of severe mitral regurgitation increases with age due to progressive myxomatous change and annular dilatation.
• Protective Factors: There are no specific known protective factors against the development of MVP. General cardiovascular health, including blood pressure control and avoidance of behaviors that contribute to heart failure, may help prevent progression of mitral regurgitation once MVP is present.

Clinical Presentation

Signs and Symptoms

• Cardinal Features: Many individuals with MVP are asymptomatic. When symptoms occur, they are often non-specific.
  • Palpitations: Common, often described as skipped beats, racing heart, or pounding. Can be due to supraventricular (e.g., PACs, PVCs) or ventricular arrhythmias.
  • Atypical Chest Pain: Vague, non-exertional, often sharp, localized to the left inframammary area, not relieved by nitrates. The mechanism is unclear but may be related to abnormal tension on papillary muscles or microvascular dysfunction.
  • Dyspnea: Exertional dyspnea is usually indicative of significant mitral regurgitation.
  • Fatigue: Non-specific, but can be reported.
  • Anxiety/Panic Attacks: A debated association, some studies suggest higher prevalence.
  • Dizziness/Syncope: Less common, may be related to orthostatic hypotension or arrhythmias.
• Early Signs: Often none, MVP is frequently an incidental finding on routine examination or echocardiography.
• Advanced Signs: Symptoms of congestive heart failure (e.g., progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema) develop if significant mitral regurgitation progresses. Symptoms of embolic events (e.g., stroke, transient ischemic attack) are rare but possible.
• Atypical Presentations: Silent MVP (no murmur or click), MVP in the setting of severe systemic illness (e.g., endocarditis, severe heart failure due to other causes).

Physical Examination

• Inspection:
  • Often normal.
  • May reveal skeletal abnormalities associated with connective tissue disorders (e.g., pectus excavatum, scoliosis, Marfanoid habitus).
• Palpation:
  • Usually normal cardiac impulse.
  • If significant mitral regurgitation is present, a hyperdynamic apex beat may be palpable.
• Auscultation (Cardinal Finding):
  • Midsystolic Click: A characteristic, high-pitched "click" sound (SMC) that occurs during mid-to-late systole. It is thought to be caused by the sudden tensing of the chordae tendineae and/or mitral leaflets as they prolapse. The timing of the click varies with preload and afterload:
    • Standing or Valsalva (decreased preload) makes the click occur earlier in systole and closer to S1.
    • Squatting or handgrip (increased preload/afterload) makes the click occur later in systole and closer to S2.
  • Late Systolic Murmur: A crescendo-decrescendo murmur that follows the click and extends to S2. It is heard best at the apex and radiates to the axilla. The murmur indicates mitral regurgitation.
    • Like the click, its timing and intensity can be altered by maneuvers.
  • Absence of Click/Murmur: Many individuals with MVP do not have an audible click or murmur, especially if the prolapse is mild or mitral regurgitation is absent.
• Special Tests:
  • Valsalva Maneuver: Decreases venous return (preload), causing the click to occur earlier and the murmur to lengthen.
  • Standing: Similar to Valsalva, decreases preload, bringing the click earlier and lengthening the murmur.
  • Squatting: Increases venous return (preload) and afterload, causing the click to occur later and the murmur to shorten/soften.
  • Handgrip: Increases afterload, causing the murmur to become louder and potentially lengthen.

Diagnostic Approach

History Taking

• Key Questions:
  • Presence and nature of palpitations, chest pain, dyspnea, fatigue, dizziness, or syncope.
  • Family history of MVP, sudden cardiac death, or connective tissue disorders.
  • History of fevers, chills, unexplained weight loss (to rule out infective endocarditis if new murmur/symptoms).
  • Previous echocardiograms or cardiac evaluations.
  • Medication history, especially stimulants or arrhythmogenic drugs.
• Red Flags:
  • New or worsening dyspnea on exertion, orthopnea, PND (suggests worsening MR and heart failure).
  • Syncopal episodes (may indicate significant arrhythmia or severe MR).
  • Acute, severe chest pain with hemodynamic instability (consider acute chordal rupture with severe MR, myocardial ischemia/infarction).
  • Fever, new murmur, or signs of systemic infection (raises suspicion for infective endocarditis).
  • Symptoms of neurological events (TIA, stroke) in a young patient (consider embolic event, though rare).

Laboratory Tests

• First-Line: No specific laboratory tests diagnose MVP.
  • Complete Blood Count (CBC): For baseline, or to evaluate for anemia if fatigue is a prominent symptom.
  • Basic Metabolic Panel (BMP): To assess renal function and electrolytes, especially if diuretics or ACE inhibitors are considered for heart failure.
  • Thyroid-Stimulating Hormone (TSH): To rule out hyperthyroidism if palpitations are prominent.
• Confirmatory: No specific lab tests; diagnosis is imaging-based.
• Monitoring:
  • B-type Natriuretic Peptide (BNP) / N-terminal pro-BNP (NT-proBNP): Useful for monitoring for the development or progression of heart failure if significant mitral regurgitation is present.

Imaging

• Recommended (Gold Standard):
  • Transthoracic Echocardiography (TTE): This is the definitive diagnostic test for MVP.
    • Diagnostic Criteria (ACC/AHA/ESC guidelines):
      • Classic MVP: Systolic displacement of one or both mitral leaflets ≥2 mm above the mitral annular plane in the parasternal long-axis view. Additionally, leaflet thickness ≥5 mm.
      • Non-Classic MVP: Systolic displacement of one or both mitral leaflets ≥2 mm above the mitral annular plane with leaflet thickness <5 mm.
    • Assessment: TTE provides information on leaflet morphology (thickening, redundancy), chordal integrity, annular size, left ventricular size and function, left atrial size, and the presence and severity of mitral regurgitation (color Doppler and quantitative methods).
• Advanced (When Needed):
  • Transesophageal Echocardiography (TEE): Provides superior imaging resolution, especially useful for:
    • Detailed assessment of leaflet pathology and chordal structures prior to surgical repair.
    • Quantifying severe mitral regurgitation when TTE is inconclusive.
    • Diagnosing infective endocarditis vegetations.
  • Cardiac Magnetic Resonance (CMR): Useful for:
    • Quantifying mitral regurgitation severity with high accuracy, particularly when TTE is inconclusive.
    • Assessing myocardial fibrosis (late gadolinium enhancement) in patients with severe MVP and non-ischemic cardiomyopathy.
    • Providing detailed anatomical assessment of the mitral valve and left ventricle.
  • Electrocardiogram (ECG): Not diagnostic for MVP, but can show:
    • T-wave inversions in inferior leads (II, III, aVF) in some patients.
    • Arrhythmias (PACs, PVCs, supraventricular tachycardia, atrial fibrillation) if present.
    • Signs of left atrial enlargement or left ventricular hypertrophy if significant MR is chronic.
  • Holter Monitor / Event Recorder: Indicated for symptomatic patients with palpitations, dizziness, or syncope to detect and characterize arrhythmias.

Management

Acute Management

• Immediate:
  • Acute Severe Mitral Regurgitation (MR): This is a surgical emergency. Often caused by chordal rupture.
    • Clinical Presentation: Acute onset dyspnea, pulmonary edema, cardiogenic shock.
    • Initial Stabilization:
      • Oxygen supplementation, ventilatory support if needed.
      • Diuretics (e.g., Furosemide IV 20-80 mg) for pulmonary edema.
      • Vasodilators (e.g., Nitroglycerin, Nitroprusside IV) to reduce afterload and improve forward flow, if blood pressure allows.
      • Inotropes (e.g., Dobutamine) if cardiogenic shock is present.
      • Intra-aortic balloon pump (IABP) counterpulsation for temporary hemodynamic support in severe cases.
    • Definitive Treatment: Emergency mitral valve repair or replacement.
• Stabilization: For less severe acute decompensations related to arrhythmias or exacerbation of heart failure, focus on rhythm control and optimization of heart failure medications.
• Emergency: Life-threatening arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation) require immediate cardioversion/defibrillation and subsequent antiarrhythmic therapy/ablation.

Chronic Management

• Pharmacological:
  • Asymptomatic MVP without Significant MR: No specific pharmacological treatment. Reassurance is key.
  • Symptoms (e.g., Palpitations, Atypical Chest Pain):
    • Beta-blockers (e.g., Metoprolol 25-50 mg BID, Atenolol 25-50 mg daily): First-line for symptomatic relief of palpitations (reducing sympathetic tone and heart rate) and atypical chest pain.
    • Antiarrhythmics: If documented sustained arrhythmias are causing significant symptoms or are high-risk (rare).
  • Significant Mitral Regurgitation (MR):
    • ACE Inhibitors/ARBs (e.g., Lisinopril 10-40 mg daily, Valsartan 80-320 mg daily): For patients with significant MR and symptoms, or asymptomatic MR with left ventricular dysfunction/dilation, to reduce afterload and slow progression.
    • Diuretics (e.g., Furosemide 20-40 mg daily/BID): For symptoms of fluid overload (dyspnea, edema) due to heart failure.
    • Aldosterone Antagonists (e.g., Spironolactone 12.5-25 mg daily): May be added for advanced heart failure.
  • Infective Endocarditis (IE) Prophylaxis:
    • Current Guidelines (AHA/ESC): Prophylaxis is only recommended for patients with MVP who have a history of infective endocarditis or who have prosthetic heart valves or prior valve repair with prosthetic material. It is NOT recommended for uncomplicated MVP or MVP with regurgitation unless these high-risk factors are present.
    • Procedure: Dental procedures involving manipulation of gingival tissue or periapical region of teeth, or perforation of oral mucosa.
    • Antibiotic Regimen: Amoxicillin 2g orally 30-60 min before procedure (or Clindamycin 600mg, Azithromycin 500mg, or Cephalexin 2g for penicillin allergy).
• Non-pharmacological:
  • Lifestyle Modifications:
    • Regular Exercise: Generally encouraged for asymptomatic patients; may be restricted in severe MR with LV dysfunction.
    • Avoidance of Stimulants: Caffeine, nicotine, decongestants, and illicit drugs can exacerbate palpitations.
    • Hydration: Adequate fluid intake can help maintain preload and reduce symptoms of orthostatic intolerance.
    • Stress Reduction: Techniques for managing anxiety can be beneficial.
  • Surgical Intervention:
    • Mitral Valve Repair (Preferred): Indicated for severe primary MR in symptomatic patients with preserved LV function, or asymptomatic patients with LV dysfunction (LVEF ≤60%), progressive LV dilation (LVEDD >40 mm), pulmonary hypertension (PHT >50 mmHg systolic at rest), or new onset atrial fibrillation. Repair is preferred over replacement due to better long-term outcomes and avoidance of prosthetic valve complications.
    • Mitral Valve Replacement: Considered when repair is not feasible or fails. Requires anticoagulation for mechanical valves.
• Monitoring:
  • Asymptomatic MVP without MR or mild MR: Follow-up echocardiography every 3-5 years.
  • MVP with moderate MR: Follow-up echocardiography every 1-2 years.
  • MVP with severe MR (asymptomatic with preserved LV function): Follow-up echocardiography every 6-12 months, or more frequently if LV function deteriorates or symptoms develop.
  • Clinical Follow-up: Regular assessment for new symptoms, changes in physical exam, or signs of complications.

Treatment Algorithms

• First-Line:
  1. Diagnosis Confirmation: Echocardiography is paramount.
  2. Asymptomatic without significant MR: Reassurance, avoid stimulants. No specific treatment.
  3. Symptomatic (Palpitations/Chest Pain) without significant MR: Beta-blockers (e.g., metoprolol 25-50 mg BID).
  4. Significant Mitral Regurgitation (MR): Optimize medical therapy for heart failure (ACEi/ARB, diuretics, beta-blockers if no severe MR with LV dysfunction).
  5. Indications for Surgical Intervention (Class I Recommendations for Primary MR):
     • Symptomatic severe primary MR with preserved left ventricular ejection fraction (LVEF >60%).
     • Asymptomatic severe primary MR with LV dysfunction (LVEF ≤60% and/or LVEDD ≥40 mm in the 2020 AHA/ACC guidelines; ESC 2021 criteria are LVEF ≤60% and/or LVESD ≥40 mm).
     • Asymptomatic severe primary MR with new-onset atrial fibrillation or pulmonary hypertension (systolic pulmonary artery pressure >50 mmHg at rest).
     • Severe MR with acute chordal rupture causing hemodynamic instability (emergency surgery).
• Second-Line:
  • For refractory symptoms: Consider alternative antiarrhythmics or electrophysiology consultation for ablation.
  • For severe MR when surgery is high-risk/contraindicated: Transcatheter mitral valve repair (e.g., MitraClip) may be an option in carefully selected patients.
• Refractory Cases:
  • Severe MR with persistent symptoms despite optimal medical therapy and surgery is not an option: Palliation of symptoms.
  • Persistent arrhythmias: Electrophysiology study and ablation.

Complications

• Common:
  • Mitral Regurgitation (MR): The most frequent and clinically significant complication. Severity varies; chronic severe MR can lead to left atrial and ventricular enlargement, pulmonary hypertension, and heart failure.
  • Arrhythmias: Supraventricular (PACs, SVT, atrial fibrillation) and ventricular (PVCs, non-sustained VT) are common. Atrial fibrillation can lead to increased risk of stroke.
• Serious:
  • Infective Endocarditis (IE): Patients with MVP (especially classic MVP with significant MR) are at slightly increased risk compared to the general population. This risk is primarily for those with thickened or redundant leaflets.
  • Chordal Rupture: Can lead to acute severe MR and sudden heart failure, requiring emergency surgery.
  • Sudden Cardiac Death (SCD): Extremely rare, but MVP has been implicated in some cases, particularly in patients with severe MR, significant LV dysfunction, complex ventricular arrhythmias, or specific genetic mutations.
  • Thromboembolism: Increased risk of stroke in patients with MVP and atrial fibrillation. The risk is also marginally elevated in MVP without AF, though much lower than with AF.
• Long-term:
  • Progressive worsening of MR over decades, potentially leading to heart failure.
  • Need for surgical intervention (repair or replacement).
  • Atrial fibrillation with its associated risks (stroke, heart failure).

Prognosis

• Factors:
  • Severity of Mitral Regurgitation: The most critical determinant. Mild MR is generally benign, while severe MR is associated with worse outcomes (higher morbidity and mortality).
  • Left Ventricular Function and Dimensions: Impaired LV function or significant LV dilation indicates progressive disease and worse prognosis.
  • Left Atrial Size: Enlarged left atrium is associated with higher risk of atrial fibrillation and adverse events.
  • Presence of Symptoms: Symptomatic MVP patients, especially with dyspnea, have a poorer prognosis.
  • Age: Older age at diagnosis of severe MR is associated with higher surgical risk and potentially worse outcomes.
  • Leaflet Morphology: Classic MVP with diffuse myxomatous degeneration tends to be more progressive.
• Survival: For asymptomatic individuals with non-classic MVP and no significant MR, the prognosis is excellent, similar to the general population. For those with severe MR, prognosis without surgical intervention is significantly worse, with a 10-year survival rate around 50-60%. Successful surgery (especially repair) can restore normal life expectancy.
• Quality of Life: Most asymptomatic patients have normal quality of life. Symptomatic patients, even with mild MVP, may experience reduced quality of life due to palpitations, chest pain, or anxiety. Quality of life significantly deteriorates with the onset of heart failure symptoms.

Prevention

• Primary: No known primary prevention strategies for the development of MVP itself, as it is often a congenital or genetically predisposed condition. Early diagnosis and management of associated connective tissue disorders may prevent some forms of secondary MVP.
• Secondary:
  • Early Detection: Regular physical examinations and echocardiographic screening in individuals with a family history of MVP or associated connective tissue disorders may allow early detection.
  • Monitoring: Regular echocardiographic surveillance in diagnosed MVP patients to detect progression of MR or LV dysfunction before symptoms arise, allowing for timely intervention.
• Tertiary:
  • Preventing IE: Strict adherence to IE prophylaxis guidelines for high-risk MVP patients.
  • Managing AF: Anticoagulation (e.g., DOACs) for MVP patients who develop atrial fibrillation to prevent stroke, guided by CHA2DS2-VASc score.
  • Surgical Intervention: Timely mitral valve repair or replacement in severe MR to prevent progression to irreversible LV dysfunction and heart failure.
  • Arrhythmia Management: Beta-blockers for symptomatic arrhythmias, or antiarrhythmics/ablation for more serious, refractory arrhythmias.

Special Populations

• Pediatric:
  • MVP can be diagnosed in children, often associated with connective tissue disorders (e.g., Marfan syndrome) or congenital heart defects.
  • Most are asymptomatic. Management focuses on monitoring for progression of MR and assessing for genetic syndromes.
  • Exercise restrictions are rarely needed unless severe MR or documented high-risk arrhythmias are present.
• Geriatric:
  • Increased incidence of degenerative calcific MVP (rather than purely myxomatous).
  • Higher likelihood of severe mitral regurgitation, often due to chordal rupture or annular calcification.
  • Comorbidities and frailty must be carefully considered when evaluating for surgical intervention.
• Pregnancy:
  • Generally well-tolerated. Most women with MVP have an uneventful pregnancy.
  • Increased blood volume during pregnancy may reduce the degree of prolapse and MR.
  • Close monitoring for symptoms of heart failure (especially with severe MR) and arrhythmias.
  • Antibiotic prophylaxis for delivery is NOT recommended for uncomplicated MVP.
• Comorbidities:
  • Connective Tissue Disorders: Management should include comprehensive care for the underlying disorder (e.g., aortic surveillance in Marfan syndrome).
  • Hypertension: Aggressive blood pressure control is crucial to reduce afterload and prevent progression of MR.
  • Coronary Artery Disease: Standard management for CAD; if concurrent, surgical revascularization may be performed during valve surgery.

Clinical Pearls

• Diagnostic:
  • Not all clicks are MVP: Physiologic clicks can occur. Conversely, not all MVP has an audible click or murmur. Echocardiography is definitive.
  • The "click-murmur" complex is highly mobile with maneuvers. This is a key distinguishing feature.
  • Differentiating from aortic stenosis (e.g., innocent flow murmur in children/young adults) based on timing and radiation.
• Treatment:
  • Reassurance is often the only intervention needed for asymptomatic MVP without significant MR.
  • Beta-blockers are highly effective for MVP-related palpitations and atypical chest pain.
  • Endocarditis prophylaxis is not routinely indicated for MVP unless specific high-risk factors (prior IE, prosthetic material) are present. Avoid unnecessary antibiotic use.
  • Mitral valve repair, when feasible, is generally superior to replacement for severe primary MR.
• Pitfalls:
  • Over-diagnosis of MVP based on minor, non-pathologic leaflet variations. Strict echocardiographic criteria must be met.
  • Unnecessary workup for atypical chest pain or palpitations in asymptomatic MVP without significant MR, which may lead to patient anxiety.
  • Initiating infective endocarditis prophylaxis without current guideline indications.

Recent Updates

• Guidelines:
  • 2020 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: Emphasizes updated criteria for surgical intervention in severe primary mitral regurgitation (LVESD threshold changed from ≥40 mm to an emphasis on LVEDD >40 mm in some contexts, but still considers LVESD ≥40 mm as a Class 2a indication for surgery). Reaffirms strong preference for repair over replacement.
  • 2021 ESC/EACTS Guidelines for the Management of Valvular Heart Disease: Similar recommendations, with specific criteria for LV dimensions (LVEF ≤60% and/or LVESD ≥40-45 mm for asymptomatic severe MR). Also highlights the growing role of transcatheter mitral valve therapies for high-risk patients.
• Evidence:
  • Ongoing research into genetic predispositions and specific molecular pathways involved in myxomatous degeneration of the mitral valve.
  • Studies continue to refine surgical techniques for mitral valve repair and explore long-term outcomes of transcatheter interventions (e.g., MitraClip).
  • Further data clarifying the true incidence of sudden cardiac death and embolic events in various subgroups of MVP.
• Controversies:
  • The role of antiplatelet therapy for embolic prevention in MVP patients without atrial fibrillation remains debated, with current guidelines generally not recommending it.
  • Optimal timing of surgery for asymptomatic severe MR with preserved LV function and borderline LV dimensions (e.g., LVEDD 35-40 mm or LVEF 60-65%).
  • The exact mechanisms underlying the association between MVP and atypical chest pain/anxiety are still not fully understood.

Key References

• Guidelines:
  • Otto, C. M., et al. (2021). 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology, 77(8), e25-e192.
  • Vahanian, A., et al. (2022). 2021 ESC/EACTS Guidelines for the management of valvular heart disease. European Heart Journal, 43(7), 561-632.
• Studies:
  • Dziurba, D., et al. (2007). Mitral valve prolapse with and without significant mitral regurgitation: a different entity? European Journal of Echocardiography, 8(6), 464-470.
  • Enriquez-Sarano, M., et al. (2004). Mitral regurgitation: a new paradigm for medical management. Mayo Clinic Proceedings, 79(11), 1386-1393.
• Reviews:
  • Boudoulas, H., et al. (2018). Mitral valve prolapse. JACC: Cardiovascular Interventions, 11(22), 2320-2331.
  • Devereux, R. B., et al. (2018). Mitral valve prolapse: Genetics and mechanisms of sudden cardiac death. Journal of the American College of Cardiology, 72(10), 1121-1134.